Javed Herra, Henrich-Lobo Rodolfo, Contorno Eli, Sudararaj Kamala P, Campbell Lia H, Greene Elizabeth D, Brockbank Kelvin G M, Rajab Taufiek Konrad
Department of Cardiovascular Surgery, Arkansas Children's Hospital, Little Rock, Arkansas, USA.
Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA.
Pediatr Transplant. 2025 May;29(3):e70063. doi: 10.1111/petr.70063.
Partial heart transplantation (PHT) is a new type of transplant that delivers growing heart valve implants for children. However, the acceptable ischemia time for PHTs remains unexplored. Therefore, the ischemia time for PHTs is empirically limited to orthotopic heart transplant (OHT) ischemia time of 4-6 h because the valves contained in OHTs are known to grow. This limits the distance from where PHT grafts can be procured. Without longer procurement distances, children who need PHT must wait a long time for suitable donor hearts. We previously demonstrated that PHTs remain viable for an ischemia time of 48 h in a rat model. Here we expand on this work in a porcine model.
Porcine pulmonary valve (PV) and aortic valve (AV) leaflets were preserved in DMEM culture medium, Belzer UW, Unisol, or HTK solution (n = 6/group) at 4°C. At preset intervals, the cellular viability was measured using the alamarBlue assay. The valves were also analyzed with flow cytometry and histology.
While the metabolic activity of the valves slowly decreased over time, there was significant cellular viability for up to 21 days of cold preservation with Belzer UW solution. Flow cytometry and histology further corroborated the results, showing cellular preservation at 7 days of ischemia time.
OHT preservation is limited to only 4-6 h because longer ischemia times are associated with primary graft dysfunction from reduced contractility of ventricular myocardial cells. In contrast, PHTs spare the native ventricles. Our results indicate that PHT grafts remain viable much longer than OHT grafts. In vivo data are needed to verify that PHT grafts can grow and function after this significantly increased ischemic time.
部分心脏移植(PHT)是一种新型移植方式,用于为儿童提供生长型心脏瓣膜植入物。然而,PHT可接受的缺血时间仍未得到探索。因此,PHT的缺血时间根据经验被限制在原位心脏移植(OHT)的4-6小时缺血时间内,因为已知OHT中包含的瓣膜会生长。这限制了获取PHT移植物的距离。如果没有更长的获取距离,需要PHT的儿童必须长时间等待合适的供体心脏。我们之前在大鼠模型中证明,PHT在48小时缺血时间内仍能存活。在此,我们在猪模型中拓展这项工作。
将猪肺动脉瓣(PV)和主动脉瓣(AV)瓣叶保存在4°C的DMEM培养基、Belzer UW溶液、Unisol溶液或HTK溶液中(每组n = 6)。在预设的时间间隔,使用alamarBlue检测法测量细胞活力。还通过流式细胞术和组织学对瓣膜进行分析。
虽然瓣膜的代谢活性随时间缓慢下降,但使用Belzer UW溶液冷藏保存长达21天时仍有显著的细胞活力。流式细胞术和组织学进一步证实了结果,显示在缺血7天时细胞得以保存。
OHT的保存仅限于4-6小时,因为更长的缺血时间与心室心肌细胞收缩力降低导致的原发性移植物功能障碍相关。相比之下,PHT保留了天然心室。我们的结果表明,PHT移植物的存活时间比OHT移植物长得多。需要体内数据来验证PHT移植物在如此显著延长的缺血时间后能否生长并发挥功能。